Hard tissues in humans are largely classified as bones and teeth. The representative diseases caused by hard tissue disorders are osteoporosis and periodontal diseases. Bones are essential for locomotion and play an important role in calcium metabolism. With age, incidences of bone fracture, osteoporosis, and severe periodontal disease accompanied by alveolar bone destruction increase significantly.
Teeth, as major components of the digestive system, are essential for mastication. Maintaining teeth in good condition is essential for satisfaction in eating and enjoying the taste of food, thereby especially increasing the quality of life for the elderly. Thus, the prevention and treatment of these aging-related diseases draw tremendous attention from societies with high percentages of elderly people.
Hard tissues undergo constant remodeling through bone formation (via osteoblast) and bone resorption (via osteoclast) and maintain homeostasis. Such metabolism is regulated by systemic hormones as well as local factors. When bone resorption rates surpass bone formation rates by a variety of factors and bone mass decreases below a critical level, bone-related diseases such as osteoporosis and periodontal disease occur.
As a biochemical index of osteoblast activity, alkaline phosphatase, Type 1 collagen, and osteocalcin are used clinically. Alkaline phosphatase is a initial index of osteoblast activity and starts to decrease as mineralization of matrix begins. Collagen is a bone matrix protein and represents approximately 90% of bone organic molecules (Schonau and Rauch, Horm. Res., 49 (suppl 5): 50-59, 1997). The majority of collagens is type 1 collagen made from a same gene present in the skin and type 5 collagen is present in a small quantity.
Collagen has a number of other functions other than as a structural protein. More specifically, it may (1) provide a place for mineral to precipitate, (2) be involved in the growth and differentiation of osteoblast, and/or (3) play an important role in mineralization and bone remodeling. Hydroxyproline represents approximately 14% of collagen contents and this formulation is relatively constant. Moreover, osteocalcin is a calcium binding protein which is expressed during the mineralization of matrix and is typically used as an index of osteoblast activity in its later stages.
In the osteoblast cells, ERK2 (Extracellular signal-regulated kinase 2) is induced by bone-active agents such as PDGF-BB, EGF, Insulin, IGF-1, Phorbol ester, and Estrogen. ERK is known to play an important role in the growth of osteoblast cells (Hipskind, B. A., Bilbe, G., Frontiers in Bioscience, 3, d804-816, 1998).
Cortex Eucommiae is the dried stem bark of Eucommia ulmoides Oliv. Its known components are mainly lignans and iridoids. In addition, erythro-/threoguaiacylglycerol, ulmoprenol, nonacosane, β-sitosterol, betulin, betulinic acid, ursolic acid and vanillic acid are also present as its components. It is known to have a variety of actions such as hypotensive, anti-hyperlipidemic, sedative and analgesic, anti-inflammatory, reticular phagocytic and diuretic effects (Chinese Materia Medica 1998). Extracts of Cortex Eucommiae are known to be very safe since their oral administrations of 15-25 g/kg to mouses did not cause death. However, their actions in the bone cells are not yet determined.